Male erectile dysfunction is one of the most common sexual dysfunctions in man. Although erectile dysfunction can be primarily psychogenic in origin, it often accompanies chronic illnesses, such as diabetes mellitus, heart disease and a variety of neurological diseases. It is estimated that about 2˜7% of the male population are impotent. Its prevalence is strongly related to age. For example, 18˜75% of the age group of 55 to 80 years is believed to be impotent.
Various treatment options for erectile dysfunction are available, such as counseling, hormone replacement therapy, self-injection or transurethral application of vasodilator agents, vacuum devices, and vascular surgery. However, these therapeutic options have several limitations such as side effects, high cost and low efficacy.
Recently, Sildenafil has been developed as a therapeutic agent for male erectile dysfuction by oral administration. Sildenafil is the first in a new class of drugs known as inhibiting phosphodiesterase-5 enzyme distributed specifically in corpus cavernosal tissues and induces relaxation of the corpus cavernosal smooth muscle cells, so that blood flow to the penis is enhanced, leading to an erection. Sildenafil has shown a response rate of around 80% in men with erectile dysfunction of organic cause.
Since sildenafil has been developed, various compounds for inhibiting phosphodiesterase-5 have been reported. Among them, pyrazolopyrimidinone compounds of formula 1 (KR Pat. No. 99-49384) were reported having better potency than that of sildenafil, based on the mechanism of inhibiting phosphodiesterase-5 and having better selectivity over phosphodiesterase-6 distributed in retina and phosphodiesterase-3 distributed in heart to reduce the side effects. Further, the pyrazolopyrimidinone compounds of formula 1 were said to be improved the solubility and the metabolism in the liver, which are very important factor affecting the rate of the absorption when administered orally.
The KR patent No. 99-49384 also disclosed a process for preparing the pyrazolopyrimidinone compounds of formula 1, comprising the steps of:                a) reacting chlorosulfonated alkoxy benzoic acid with a primary amine to obtain sulfonamide-substituted benzoic acid;        b) reacting the obtained sulfonamide-substituted benzoic acid with pyrazolamine in the presence of activating reagent of carboxylic group or coupling agent of carboxylic group with amine group to obtain corresponding amide compound; and,        c) performing an intramolecular cyclization of the obtained amide compound to obtain the pyrazolopyrimidinone compound of formula 1.        
This reaction is represented as follows. 
However, the said process has several disadvantages. First, the reaction of the sulfonamide-substituted benzoic acid with pyrazolamine in the step b) requires the expensive coupling reagent or activation reagent such as trichloro benzoyl chloride and EEDQ (N-ethoxycarbonyl-2-ethoxy-1,3-dihydroquinoline). Second, the yield of the step a) in which the chlorosulfonated alkoxy bonzoic acid reacts with a primary amine to produce sulfonamide-substituted benzoic acid is somewhat low, and thus, reduces the total yield of the process.
Leading to the present invention, the intensive and thorough research for efficiently preparing the pyrazolopyrimidinone compound useful for the treatment of impotence, carried out by the present inventors aiming to avoid the problems encountered in the prior arts, resulted in the finding that the pyrazolopyrimidinone compound can be prepared under mild condition in high yield, with high purity and in a economic manner by chlorosulfonation, amination with a primary amine and intramolecular cyclization of a pyrazolamide compound obtained by the reaction of alkoxy benzoic acid with pyrazolamine.
Therefore, it is an object of the present invention to provide a process for preparing pyrazolopyrimidinone derivatives of formula 1 and pharmaceutically acceptable salts thereof.